Rates of substance use (SU) and substance use disorders (SUD) among adolescents in the US have reached epidemic proportions. An effective early prevention strategy that targets adolescents at high risk for SU/SUD by virtue of family history (FH+) would make a significant and cost-effective contribution. While this relationship is not yet well understood, recent research, including our own NIDA-funded Pilot Study (SUD and Decision-Making: A Pilot Imaging Study of Parents and Children; R21 DA031975; Principal Investigator: C Hoven) has begun to identify deficits in cognitive control, measured both behaviorally and neurobiologically, as key factors involved in adolescent SU/SUD. Our Pilot findings reveal consistently strong hyperactivity and reduced connectivity in the FH+ group in neural circuits thought to play key roles in decision making, reward and addiction. These changes are observed prior to an individuals' exposure to psychoactive substances, thus, reflecting pre- existing vulnerabilities. The findings from our Pilot Study are therefore compellin. The proposed Adolescent Brain Study (ABStudy), using MMRI's (multimodal imaging) at baseline and at 36 months, combined with three formal cognitive tasks, and a developmentally-oriented study design, which includes assessments every three months, has the goal of contributing to the open questions while improving our understanding of FH+ children and their neurobehavioral development. We will combine cutting edge MMRI with the latest neurocognitive laboratory tasks to extend and build upon our Pilot Study, both longitudinally and methodologically, drawing on a non-clinical, epidemiological sample, which has been extensively characterized (5R01DA023733-05 and 5R01DA024029-05; Principal Investigator: C. Hoven). Specifically, we will: 1) Identify the relationship between parental SUD history (FH+/-) and neurobehavioral indicators of cognitive control (behavioral and brain structure/functioning) in their children during early adolescence, 2) Examine the prospective association between FH+/- status and baseline neurobehavioral indicators of cognitive control with subsequent onset and progression of problematic SU trajectories from early adolescence through mid- adolescence, 3) Examine longitudinally associations between FH+/- status, in the development of neurobehavioral indicators of cognitive control, and onset and progression of problematic SU trajectories from early adolescence through mid-adolescence. We will study 150 substance nave individuals, from early adolescence (ages 12-14), who come equally from FH+/FH- families, and follow them through mid-adolescence (ages 15-17). Importantly, this study will examine the neurobehavioral dimensions while simultaneously, possibly for the first time in an adolescent imaging study, taking into account socio-cultural contextual factors, known to contribute to adolescent SU.